Typhoid fever is perceived to be a major problem in India, but its true incidence is uncertain. In preparation for future field trials of typhoid vaccines, this research is establishing two field sites, an urban site in Delhi and a rural site in Chingleput near Madras, to monitor typhoid incidence in cohorts of subjects. The site in Delhi comprises a population of about 19,000 persons, while that in Chingleput has nearly 33,000 persons. During the initial six months of surveillance in Delhi site, the data project an annual incidence of up to 4.6 cases per 1,000, while during the initial 3 months of surveillance in Chingleput, the data project an incidence of 1 per 1,000. All cases of typhoid are being followed for up to 3 months to determine typhoid-related disability, and case-control studies are nested within these cohorts to assess foods, water sources, and hygienic practices associated with typhoid risk, as well as the role of H. pylori coinfection in influencing this risk. Future serosurveys will enable determination of the age-specific seroprevalence of anti-d antibodies, to provide complementary evidence addressing the burden of typhoid.